Viruses propagate by living within the cells of higher-order vertebrates. Accordingly, they have evolved to specifically avoid the host immune system. Virus survival is dependent upon strategies that can evade, suppress, counteract, or otherwise circumvent host responses to a foreign antigen. These host responses are a powerful element of evolutionary pressure; all eukaryotic viruses existing today contain remnants of their battles with the host immune system, as evidenced by the presence of viral-encoded proteins that suppress the immune response or allow the virus to avoid immune system detection.
The specific strategy or strategies used by a virus varies dramatically according to its genome capacity. Viruses with small genomes ensure their survival by exploiting weaknesses or gaps in the host immune repertoire to avoid detection. Alternatively or additionally, small viral genomes replicate rapidly, effectively outpacing the host immune response. Larger DNA viruses (e.g., adenoviruses, herpesviruses, iridoviruses, and poxviruses) specifically encode proteins that function to protect the virus from immune recognition and/or clearance by the infected host. Such “subversive” viral proteins are useful therapeutics for the treatment of inflammatory and autoimmune disorders. Poxviruses, in particular, have been a rich source of such immunomodulatory proteins.
The Yatapoxvirus genus of poxviruses includes Tanapox virus (TPV), Yaba monkey tumor virus (YMTV), and Yaba-like disease (YLD) virus (Knight et al., Virology 172:116-124, 1989). Both TPV and YMTV contain a linear double-stranded, approximately 145 kbp DNA genome (Essani et al., Microbial Pathogenesis 17:347-353, 1994; Knight et al., supra). TPV produces a mild disease in humans, characterized by transient fever, one or more nodular skin lesions, and regional lymphadenopathy, while YMTV causes benign tumors in monkeys and humans (Paulose et al., Microbial Pathogenesis 25:33-41, 1998; Amano et al., Journal of General Virology 76:1109-1115, 1995). A 38 kDa secreted glycoprotein from TPV-induced cells has been reported to specifically bind and neutralize three human cytokines, namely interferon-γ, interleukin-2, and interleukin-5 (Essani et al., supra).
It would be useful to identify novel viral immunomodulatory genes and polypeptides for the treatment of immunological disorders.